Transthyretin amyloidosis and superficial siderosis of the CNS

Objective: To describe a previously unreported clinical and radiologic pres entation of hereditary transthyretin (TTR)-related amyloidosis. Background: Unexplained cerebellar ataxia, pyramidal syndrome, and hearing loss are ob served in some patients with TTR-related amyloidoses. Methods: We performed clinical, radiologic, and pathologic examinations of three family members with TTR-related (Ala36Pro) amyldidosis. Results: The patient was a 69-year -old woman with vitreal amyloid deposits, progressive sensorineural deafnes s, cerebellar ataxia, pyramidal syndrome, and recurrent transient neurologi c symptoms. Cranial MRI showed symmetric thin rims of low signal intensity in T2- and T2*-weighted images in the cortex of the sylvian fissures, of th e cerebellar hemispheres and vermis, and in the quadrigeminal plate consist ent with superficial siderosis of the CNS. Her older daughter had vitreal a myloid deposits, acute Brown-Sequard syndrome? at C4, acute sensorineural d eafness, and recurrent transient neurologic symptoms. Cranial MRI at age 48 revealed a rim of low signal intensity in T2- and T2*-weighted images in t he superior vermis folia and the right sylvian cortex. In addition, two sma ll hemosiderin deposits were seen in the left parietal cortex. Lumbar punct ure yielded colorless CSF with increased ferritin content and was followed by fourth ventricle hemorrhage. Cranial MRI 11 months later showed progress ion of brain hemosiderin deposits. The younger daughter had vitreal deposit s, sensorimotor polyneuropathy, and acute sensorineural hearing but no evid ence of siderosis on cranial MRI. She died at age 43 years of posterior fos sa subarachnoid hemorrhage, and the neuropathologic examination showed amyl oid deposition in the leptomeningeal spaces and vessels. Conclusion: Transt hyretin-related amyloidosis may cause superficial siderosis of the CNS thro ugh subarachnoid bleeding related to meningovascular amyloid deposition.